17beta-(1&#39;-alkoxy-ethylidene-amino) steroids



United States Patent Ofifice 3,029,262 Patented Apr. 10, 1962 wherein the linkages between the 5 and 6 and 16 and 17 carbon atoms, respectively, are either single or double bonds, and R is hydrogen or an aor B-oriented methyl group. It will be understood, of course, that when R is methyl and there is a double bond between carbon atoms 16 and 17, this methyl group will not be oriented. These compounds, for example, pregn-S-ene-3/3-ol-20-one, 51xpregnane-fvB-ol-ZO-one, 16a-methyl-pregn-5-ene-3fl-ol-20 one, lfi-methyl-pre -5-ene-3fi-ol-20-one, IGor-methyl-Sapregnane-BB-ol-ZO-one, lG-methyl-pregna-S,16-diene-3r3- ol-20-one, when reacted with an alcohol R'OH in which R is a lower alkyl radical, particularly methyl or ethyl, and anhydrous hydrazoic acid in the presence of hydrogen chloride, are converted to 17-alkyl-acetimido-derivatives having the general formula the starting material a compound which has already been esterified in the 3-position.

The reaction may be carried out by dissolving the starting steroid compound and anhydrous hydrazoic acid in an inert organic solvent, such as chloroform, and mixing this solution with the appropriate alcohol saturated with gaseous hydrogen chloride. The reaction temperature is preferably kept between 0 and 30 C.

The following examples are set forth as illustrative of but not as limiting the invention:

Example 1 A solution consisting of 1 part pregn-5-ene-3;3-ol-20- one in 10 parts of a 1.6 molar chloroform solution of anhydrous hydrazoic acid is added to 10 parts of a 27% ethanolic solution of gaseous HCl, at a temperature of about 0 C. After the addition, the solution is shaken for 1 hour at room temperature, then poured into 30 parts of a 40% aqueous solution of potassium carbonate.

The chloroform is partially removed, the solution is washed with water to neutrality, the solvent is evaporated completely in vacuum and the residue is crystallized from methanol. 0.8 part of l7,8-(1'-ethoXy-ethylidene-arnino)- androst-S-ene-BB-ol are obtained, M.P. 169171.5 C.; [a] =-27, infrared maxima at 5.99 8a. Conventional acetylation with pyridine and acetic anhydride results in the 3-acetate, M.P. 132-133" C.; [a] =-28, infrared maxirna at 2.78 5.99 1 8.1

Following this procedure and starting with 5wpregnane-313-ol-20-one, there was prepared l7B-(l'-ethoxyethylidene-amino)-5aandrostane-3Bol, MP. 174-176 C.; [a] =-{46; infrared maxima at 598 8.01 1. and its S-acetate, Ml. 129131' C.; [a] =+41; infrared maxima at 5.78 r, 5.98 and 8.1a.

From 1Ga-methyl-pregn-S-ene-SB-ol-ZO-one, there was prepared 16cc methyl-17M1-ethoXy-ethylidene-amino)- androst-5-ene-3fl-ol, M.P. l74-l76 C.; [m] =51; infrared maxima at 4.78 5.97 8

From SB-acetOXy-I-111ethyl-pregn-S-ene-ZO-one, there was prepared 3/3-acetoXy-16(3-methyl-17B-(1'-ethoXy-ethylidene-amino)-androst-5-ene, Ml. l26129 C; [a] +8; infrared maxima at 5.78 5.98 8a..

From 3fi-acetoxy-16,8-rnethyl-5u-pregnane-20-one, there was prepared 3,8-acetoXy-l6 8-methyl-17fi-(1'-ethoxy-ethylidene-amino)-5a-androstane, M.P. 131l32 C.; [a] +23; infrared maxima at 5.78 5.98,, 8,u.

From 16a-methyl-Su-pregnane-Sfl-oI-ZO-One, there was prepared l6u-methyl-17fi-( l -ethoXy-ethylidene-amino) 5ct-androstane-3f3-ol, MP. 157-159 C.; [m] =+15, infrared maxima at 5.98 8.01 and its 3-acetate, M.P. l55157 C., [a] =+11; infrared maxima at 5.75 r, 5.97,u, 8 1..

From 16-methyl-pregna-5,l6-diene-3B-ol-20-one, there was prepared 16-methyl-17-( 1-ethoxy-ethylidene-amino)- androsta-5,16 diene-BB-ol, MP. l48-150 C; [111 -143; infrared maxima at 6.02 6.19 8 d.

Example 2 Following the procedure outlined in Example 1 but using methanol instead of ethanol, 17,B-(1'-methoxyethylidene-amino)-androst-5-ene-3/3-ol is obtained from pregn-5-ene-3[3-ol-20-one, M.P. 166169 C.; [a] --25"; infrared maxima at 5.99,:4, 8 1.

By the conventional esterification reaction also described in Example 1, there is obtained the 3-acetate, MP. -138 C.; [a] =25, infrared maxima at 5.75n, 538a, 8.1a.

From 16winethyI-Sa-pregnane-Zlfl-ol-ZO-one, there was prepared 1 6a-methyl- 17 8- 1-methoxy-ethylidene-arnino a-androstane-3fi-ol, MP. l55158 C.; [a] =+18; infrared maxima 5.98 1, 8.01 and its 3-acetate, Ml. 173174 (3.; {a] =+17; infrared maxima 5.75 5.97 1, 801p" From 16-methyl-pregna-5,l6-diene-3fi-ol-20-one there was prepared 16 methyl 17 (1'-methoxy-ethylidene amino) androsta-5,16-diene-3B-ol, M.P. 193-196 C., [a] =153, infrared maxirna at 6.0211, 6.19;, 8

The present compounds may be mixed with conventional pharmaceutical carriers, either liquid or solid and administered orally. In association with a sterile, nonpyrogenic liquid carrier, they are also suitable for parenteral administration.

The present application is a continuation-impart of our co-pending application Serial No. 75,091 filed December 12, 1960, now abandoned.

We claim:

1. A process of preparing compound having the formula 5 ewe Ii wherein X, Y, R and R have the same meaning as above with anhydrous hydrazoic acid and an alcohol ROI-I in which R has the same meaning as above.

2. Compounds having the formula wherein X and Y are each selected from the group consisting of single and double bonds, R is a member selected from the group consisting of hydrogen, an a-methyl group and ,B-rnethyl group, R is a lower alkyl group, and R is a member selected from the group consisting of hydrogen and an acyl radical derived from a lower alkanoic acid.

3. 17,3 (1 ethoxy-ethyIidene-amino)-androst-5-ene- 3,8-ol.

4. 3B acetoxy 17/3 (1' ethoxy-ethylidene-amino)- androst-S-ene.

5. 1718 (1-methoxy-ethylidene-amino)-androst-5-ene- 35-01.

6. 35 acetoxy 17f! (1'-methoXy-ethylidene-amino)- androst-S-ene.

7. 17B (1' ethoxy-ethylidene-amino) -5a-androstane- 313-01.

8. 3B acetoxy 17;8(1'-ethoxy-ethylidene-amino)-5aandrostane.

9. 3 3 acetoxy l6fi-methyl-17fl-(1'-ethoXy-ethylideneamino)-androst-5-ene.

10. 3;.8 acetoxy-lfifl-methyl-17fi-(1'-ethoxy-ethylideneamino)-5a-androstane.

11. methyl 17 8-(1-ethoxy-ethylidene-amino)- androst-5-ene-3fi-ol.

12. 3B acetoxy-l6u-methyI-17 8-(1'-ethoXy-ethylideneamino)-androst-5-ene.

13. 16a methyl-17fl-(1'-ethoxy-ethylidene-amino)-5uandrostane-Sfi-ol.

14. 3B acetoxy-16a-rnethyl- 17B-(1-ethoxy-ethylideneamino) -5 a-androstane.

15. 16a methyl 17;8-(1'-methoxy-ethylidene-amino)- 5u-androstane-3B-o1.

16. 3,8 acetoxy 16oz methyl-%1'-methoxy-ethylidene-amino) -5 a-androstane.

17. 16 methyl 17 (1 ethoxy ethylidene-amino)- androsta-S,16-diene-3fl-ol.

18. 16 methyl 17 (1'-methoxy-ethylidene-amino)- androsta-S,16-diene-3fl-ol.

None references cited.

UNITED STATES PATENT OFFICE CERTIFICATION OF CORRECTION Patent No. 3,029,262 April 10, 1962 Pietro de Ruggieri et a1 It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below Column 1, lines 45 to 56, the formula should appear as shown below instead of as in the patent:

Signed and sealed this 9th day of October 1962.

(SEAL) lhttest:

ERNEST W. SWIDER DAVID L. LADD Attesting Officer Commissioner of Patents 

2. COMPOUNDS HAVING THE FORMULA 